An antiretroviral drug improves the cognitive ability of mice with Down syndrome

O lamivudinean antiretroviral drug commonly used for the treatment of HIV, improves cognitive ability in mice with Down’s syndromeaccording to a joint study by the Center for Genomic Regulation (CRG) and the AIDS Research Institute IrsiCaixa. The finding was published today in the journal Journal of Cellular and Molecular Medicine.

While clinical trials are needed to confirm a similar effect in humans, the results reflect the potential to use pharmacological interventions like this compound, or others that block the same therapeutic target, as a treatment to improve the cognitive impairment of people with said syndrome.

To promote independent living, people with Down syndrome undergo psychosocial interventions such as cognitive stimulation therapy, one of the only treatment options available today. Yes well there are no drugs yet, The results of this study point to a possible route of treatment with drugs and local retrotransposons as a potential therapeutic target.

“Our work aims to support people with Down syndrome and their families by offering them more options to live independently, particularly individuals affected by early-stage Alzheimer’s disease,” he says. Mara DiessenCRG researcher and co-author of the study.

A new hope

O retrotransposons they are DNA segments that change location within the genome itself; To do this, they create RNA copies of themselves to get out of the area where they are located, and later become DNA again to reinsert themselves into the genome, but elsewhere. If, by chance, they are positioned in regions that promote genes associated with neurodegenerative diseases, these segments potentiate their activity.

Also, retrotransposons have some similarities with HIV, as they also need to pass from DNA to RNA (and vice versa) to make copies of themselves. Thus, the researchers thought that the use of molecules capable of inhibiting HIV replication – such as the enzyme reverse transcriptase– could also work to block retrotransposons.

Lamivudine can be used to slow cognitive decline in people with Down syndrome /CRG/Omar Jamshed

“Both HIV and retrotransposons need the same molecule to make copies of themselves: the enzyme reverse transcriptase”, he explains. Bonaventura Cloteto, director of IrsiCaixa. “Lamivudine, an inhibitor of this enzyme, has been shown to decrease retrotransposon activation in aged mice. Therefore, we think that its use could also be useful to counteract the cognitive deterioration associated with Down syndrome”, he adds.

Causes and consequences of Down syndrome

Down syndrome is a condition caused by a third copy (instead of two) on chromosome number 21 in the genome. This extra copy causes an intellectual disability that can range from mild to moderate and affects memory, attention and speech. Also, as adults, people with Down syndrome experience accelerated aging which translates into premature cognitive deterioration.

People with this syndrome also are at higher risk of Alzheimer’s since chromosome 21 contains the genes for a protein (amyloid precursor) associated with this disease. This protein can accumulate in the brain and alter brain function. This phenomenon is common in adults over 40 years of age with this condition.

The mouse study and the way forward

To demonstrate this, the research team worked with mice for four months, where one group was treated with lamivudine while the other received only water. The team then carried out several behavioral experiments to check locomotor activity, recognition memory and anxiety. Thus, they found that mice given this drug had better cognitive abilities.

We continue to need pharmacological treatments that consistently help improve memory, attention and language functions, or prevent cognitive decline associated with aging.

Mara Dierssen, CRG

“We continue to need pharmacological treatments that consistently help improve memory, attention and language functions, or prevent cognitive decline associated with aging. This study is another step towards changing this situation, as it reveals that retrotransposon activity is an interesting mechanism that needs to be studied not only in aging but also in neurodevelopmental disorders”, concludes Dierssen.

Lamivudine is a prescription drug approved by US and EU medical authorities to treat HIV infection in adults and children. The next step for the research team is to start clinical trials with the drug for people with Down syndrome and Alzheimer’s disease.